As a non-β-lactam inhibitor, one of diazabicyclooctanone compounds, avibactam may inhibit type A (including ESBL and KPC) and type C β-lactamases. When administered in combination with various types of cephalosporins and carbapenem antibiotics, avibactam has a broad spectrum activity against bacteria, particularly has a significant activity against the Escherichia coli and Klebsiella pneumoniae containing ultra-broad spectrum R-lactamases, Escherichia coli containing excessive AmpC enzyme, and Escherichia coli containing both AmpC and ultra-broad spectrum β-lactamases. Avibactam (I), with the CAS No. 1192491-61-4 and the chemical name of [(1R,2S,5R)-2-(aminocarbonyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl] sodium sulphate, has a structural formula represented in Formula I:

In patent literatures CN103649051A, CN105294690A, CN106866668A, WO2012086241, U.S. Pat. Nos. 8,148,540, 9,284,273, and 9,567,335, avibactam (I) was all prepared by using (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (II) as an intermediate. The (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (II) was debenzylated under palladium-on-carbon catalyzation in the presence of different reducing agents (such as hydrogen, triethylsilane, sodium formate, and hydrazine hydrate), then sulfated by the sulfur trioxide complex and salinized into quaternized ammonium, followed by ion exchange to obtain avibactam (I), as shown in Scheme 1.

Various processes for preparing (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (II) are mainly divided into two schemes: amidation followed by urea cyclization, and urea cyclization followed by amidation, as shown in Scheme 2:

The patents CN103649051A and CN105294690A adopted the scheme of amidation followed by urea cyclization. 5R-[(benzyloxy)amino]piperidine-2S-carboxylate oxalate (III) as the raw material was amidated in a methanol solution of ammonia gas or an aqueous ammonia alcohol solution and the reaction mixture was filtered to remove annomium oxalate, the ammonium oxalate filter cake was washed with methanol and the resulting methanol solution was concentrated, the product was extracted with methylbenzene, and recrystallized with an appropriate solvent to obtain (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide (yield: 68-99%); then, a carbonylation reaction between carbonyl diimidazole and benzyloxylamine was carried out under the protection of the amino on the piperidine ring of the resulting (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide with 9-fluorenylmethyl chloroformate (FMOC-Cl), and after the removal of the protection group on the piperidine ring using diethylamine urea cyclization was carried out to obtain (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (II) (yield: 90%, total yield: 61.2-89.1%). In that preparation process, the post-amidation treatment is complicated; and the protecting agent 9-fluorenylmethyl chloroformate used for urea cyclization is expensive. Besides, the 9-fluorenylmethyl chloroformate and the carbonyl diimidazole only provide one carbonyl, such that the reaction has a poor atom economy, which does not facilitate environment protection and cost reduction. Further, direct urea cyclization of (2S,5R)-5-[(benzyloxy) amino]piperidine-2-carboxamide using triphosgene and carbonyl diimidazole without protection of the amino on the piperidine ring has a low yield (50-56%) without industrial value.
Further, the patents CN102834395A, CN103649051A, CN103328476A, CN106279163A, CN106565712A, U.S. Pat. Nos. 9,284,273, and 9,567,335 all relate to a process of urea cyclization followed by amidation. 5R-[(benzyloxy) amino]piperidine-2S-carboxylate oxalate (III) as the raw material was urea cyclized using triphosgene-organic base, carbonyl diimidazole or other carbonylation agents, then hydrolyzed in an alkaline condition such as the aqueous lithium hydroxide to obtain (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid; then, the carboxyl was activated into anhydride using trimethylacetyl chloride or other agents and then the anhydride was amidated using the aqueous ammonia to obtain (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (II), with a total yield of 34.5-65.5%. The (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formate obtained by urea-cyclization has a low reactivity, which cannot be directly amidated in a methanol solution of ammonia gas. Instead, to be effectively amidated, the ester group needs to be hydrolyzed into the carboxyl, and then the carboxyl is activated into the anhydride. This process has a complicated operation procedure and a poor atom economy, which thus does not facilitate environment protection and industrial production.